Schneider M
Clinic for Endocrinology, Diabetology and Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany.
Lupus. 2007;16(3):221-6. doi: 10.1177/0961203306075615.
The European League Against Rheumatism (EULAR)'s guidelines for lupus state that mycophenolate mofetil has at least equivalent efficacy to and less toxicity than cyclophosphamide for the short-and medium-term treatment of lupus nephritis but that long-term data are available only for cyclophosphamide. New therapies are needed to reduce toxicity and the need for steroids and to offer the possibility of cure. Therapies under investigation include other immunosuppressive agents, anti-cellular therapies, drugs that modify cell-cell interactions, (anti-)cytokine therapy, hormone therapy and lupus-specific immunomodulation. Rituximab has shown promise in patients refractory to conventional immunosuppression, which suggests that targeting B cells may be successful. Other anti-cell therapies include epratuzumab, belimumab and alemtuzumab. Anti-cytokine approaches include tumour necrosis factor alpha blockade with infliximab, anti-interleukin 6-receptor therapy with tocilizumab and interferon-alpha blockade. As antidouble-stranded DNA antibodies correlate with flares of lupus nephritis, they may represent another therapeutic target--as do monocyte chemoattractant protein-1 and protein kinase CK2. Therapeutic options to prevent damage in lupus nephritis include non-immunosuppressive treatments aimed at reducing cardiovascular risk (such as statins, angiotensin-converting enzyme inhibitors and aspirin). As was the case with rheumatoid arthritis, a change in therapeutic aims--from survival through prevention of renal failure to induction of remission--may modify outcomes. EULAR's guidelines state that renal biopsy is the best monitor of clinical outcome in lupus nephritis, as immunological tests have limited predictive value. Measurement of urinary mRNA for cytokine and growth factor genes may provide a more sensitive, non-invasive method of monitoring therapeutic response.
欧洲抗风湿病联盟（EULAR）的狼疮指南指出，在狼疮性肾炎的短期和中期治疗中，霉酚酸酯的疗效至少与环磷酰胺相当，且毒性低于环磷酰胺，但长期数据仅适用于环磷酰胺。需要新的疗法来降低毒性、减少对类固醇的需求并提供治愈的可能性。正在研究的疗法包括其他免疫抑制剂、抗细胞疗法、改变细胞间相互作用的药物、（抗）细胞因子疗法、激素疗法和狼疮特异性免疫调节。利妥昔单抗已在对传统免疫抑制难治的患者中显示出前景，这表明靶向B细胞可能会成功。其他抗细胞疗法包括依帕珠单抗、贝利木单抗和阿仑单抗。抗细胞因子方法包括用英夫利昔单抗阻断肿瘤坏死因子α、用托珠单抗进行抗白细胞介素6受体治疗和阻断干扰素α。由于抗双链DNA抗体与狼疮性肾炎的发作相关，它们可能代表另一个治疗靶点——单核细胞趋化蛋白-1和蛋白激酶CK2也是如此。预防狼疮性肾炎损伤的治疗选择包括旨在降低心血管风险的非免疫抑制治疗（如他汀类药物、血管紧张素转换酶抑制剂和阿司匹林）。与类风湿关节炎一样，治疗目标的改变——从通过预防肾衰竭生存到诱导缓解——可能会改变治疗结果。EULAR的指南指出，肾活检是狼疮性肾炎临床结果的最佳监测方法，因为免疫检测的预测价值有限。测量细胞因子和生长因子基因的尿mRNA可能提供一种更敏感、非侵入性的监测治疗反应的方法。
